The quantitative research of wetland landscape fragmentation in the middle reaches of the Heihe River is important for the wetland and oasis sustainable development in the Hexi Corridor. Based on the data of remote sensing and GIS, we constructed the type change tracker model with sliding window technique and spatially morphological rule. The suitable scale and optimum scale of the fragmentation model of wetland landscape in the middle reaches of the Heihe River were determined by the area frequency statistics method, Chi-square distribution normalized scale variance, fractal dimension and diversity index. By integrating type change tracker model and the optimum scale with GIS spatial analysis, the spatial distribution characteristics of wetland landscape fragmentation in different periods and the related spatial-temporal change process were clarified. The results showed that(1) the type change tracker model, which analyzes the spatial pattern of wetland fragmentation on the pixel level, is better than the traditional wetland fragmentation analysis on the landscape and patch levels;(2) The suitable scale for the wetland fragmentation ranged from 150 m×150 m to 450 m×450 m and the optimum scale was 250 m×250 m in the middle reaches of the Heihe River; and(3) In the past 35 years, the total wetland area decreased by 23.2% and the fragmentation of wetland markedly increased in the middle reaches of the Heihe River. The areas of core wetlands reduced by 12.8% and the areas of perforated, edge and patch wetlands increased by 0.8%, 3.1% and 8.9%, respectively. The process of wetland fragmentation in the research region showed the order of core wetland, perforated or edge wetland, patch wetland or non-wetland. The results of this study would provide a reference for the protection, utilization and restoration of limited wetland resources and for the sustainable development of the regional eco-environment in the Heihe River Basin. The quantitative research of wetland landscape fragmentation in the middle reaches of the Heihe River is important for the wetland and oasis sustainable development in the Hexi Corridor. Based on the data of remote sensing and GIS, we constructed the type change tracker model with sliding window technique and spatially morphological rule. The suitable scale and optimum scale of the fragmentation model of wetland landscape in the middle reaches of the Heihe River were determined by the area frequency statistics method, Chi-square distribution normalized scale variance, fractal dimension and diversity index. By integrating type change tracker model and the optimum scale with GIS spatial analysis, the spatial distribution characteristics of wetland landscape fragmentation in different periods and the related spatial-temporal change process were clarified. The results showed that (1) the type change tracker model, which analyzes the spatial pattern of wetland fragmentation on the pixel leve l, is better than the traditional wetland fragmentation analysis on the landscape and patch levels; (2) The suitable scale for the wetland fragmentation ranged from 150 m × 150 m to 450 m × 450 m and the optimum scale was 250 m × 250 m in the middle reaches of the Heihe River; and (3) In the past 35 years, the total wetland area decreased by 23.2% and the fragmentation of wetland markedly increased in the middle reaches of the Heihe River. The areas of core wetlands reduced by 12.8% and the areas of perforated, edge and patch wetlands increased by 0.8%, 3.1% and 8.9%, respectively. The process of wetland fragmentation in the research region showed the order of core wetland, perforated or edge wetland, patch wetland or non -wetland. The results of this study would provide a reference for the protection, utilization and restoration of limited wetland resources and for the sustainable development of the regional eco-environment in the Heihe River Basin.