Objective: To investigate the effect of α1-antitrypsin combined with bone marrow mesenchymal stem cells on retinopathy in diabetic rats and its mechanism. Methods: A model of diabetic retinopathy was established by intraperitoneal injection of streptozotocin. The 30 Wistar rats successfully modeled were randomly divided into a model group, a bone marrow mesenchymal stem cell group and a combined group (α1-antitrypsin combined with bone marrow Mesenchymal stem cells), the blood glucose and serum insulin levels of diabetic rats were measured 4 weeks after treatment. Enzyme-linked immunosorbent assay (ELISA) for measuring serum inflammatory factors IL-1β, IL-6 and TNF-α in rats. Observing the pathological morphology of rat retina under hematoxylin-eosin staining (HE). TUNEL staining to observe the apoptosis of rat retinal nerve cells. Immunohistochemical method to detect the expression level of CD45 in retinal tissue. Real-time fluorescence quantitative PCR was used to detect the expression of retinal vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1α (HIF-1α), and angiotensin Ⅱ (ANGⅡ) mRNA. Western blot was used to detect the expression of p38 MAPK/NF-κB signaling pathway-related proteins in the retinal tissue of each group of rats. Results: Compared with the control group, the rats in the model group had increased blood glucose, decreased insulin levels, increased serum IL-1β, IL-6, and TNF-α levels, and had obvious lesions in the retina. CD45 showed high expression in retinal tissue, VEGF, HIF-1α, ANGⅡ mRNA expression increased, p-p38, p-p65, p-IκBα protein expression increased (P<0.05). Compared with the model group, the bone marrow mesenchymal stem cell group and the combined group have decreased blood glucose, increased insulin levels, and decreased serum IL-1β, IL-6 and TNF-α levels. Retinopathy is improved, apoptosis of retinal nerve cells is reduced, CD45 expression in retinal tissue is reduced, VEGF, HIF-1α, ANGⅡ mRNA expression is decreased, and p-p38, p-p65, p-IκBαprotein expression is decreased. Compared with the bone marrow mesenchymal stem cell group, the effect of the combined group was more obvious (P<0.05). Conclusion: 1-antitrypsin combined with bone marrow mesenchymal stem cell transplantation can improve the degree of retinopathy in diabetic rats. The mechanism may be related to the inhibition of p38 MAPK/NF-κB signaling pathway.