Aim:The aim of the present study was to further elucidate the mechanism of theprotective role of fluvastatin on diabetic nephropathy.Methods:Streptozotocin-induced diabetic rats were treated daily with fluvastatin (4 mg/kg body weight) bygavage.The animals were killed 4 weeks later and urine and blood samples werecollected.The kidney tissues were removed and subjected to the followingexperiments.Rat glomerular mesangial cells (GMC) were cultured under normalglucose (5.5 mmol/L),high glucose (HG,30 mmol/L),HG+AG490 (10 μmol/L),orHG with fluvastatin (1 μmol/L).Glomeruli or the GMC lysate was immunoprecipi-tared and/or immunoblotted with antibodies against Janus kinase 2 (JAK2),SH2-domain containing tyrosine phosphatase-1 (SHP-1),phosphospecific SHP-2,andsignal transducer and activators of transcription (STAT),respectively.Trans-forming growth factor-β(TGF-β1) mRNA was measured by RT-PCR.The proteinsynthesis of TGF-β1 and fibronectin in the culture medium of GMC was detectedby ELISA.Results:The phosphorylation levels of JAK2,STAT1,STAT3,andSHP-2 increased significantly,and SHP-1 phosphorylation was reduced in glom-eruli of diabetic rats.Treatment with fluvastatin reduced phosphorylation levelsof JAK2,STAT1,STAT3,and SHP-2 in glomeruli of diabetic rats,but it had noeffect on the dephosphorylation of SHP-1.The exposure of GMC to 30 mmol/Lglucose caused the activation of JAK2,STAT1,STAT3,and SHP-2.It upregulatedTGF-β1 expression and increased protein synthesis of fibronectin.These highglucose-induced changes were suppressed by fluvastatin,as well as AG490,aJAK2 inhibitor.Conclusion:The regulation of the phosphorylation of JAK/STATby fluvastatin may be responsible for its renal protective effects on diabeticnephropathy. Aim: The aim of the present study was to further elucidate the mechanism of the protective role of fluvastatin on diabetic nephropathy. Methods: Streptozotocin-induced diabetic rats were treated with with fluvastatin (4 mg / kg body weight) bygavage. The animals were killed 4 weeks later and urine and blood samples werecollected.The kidney tissues were removed and subjected to the followingexperiments. Rat glomerular mesangial cells (GMC) were cultured under normal glucose (5.5 mmol / L), high glucose (HG, 30 mmol / L), HG + AG490 (10 μmol / L) orHG with fluvastatin (1 μmol / L). Glomeruli or the GMC lysate was immunoprecipitated and / or immunoblotted with antibodies against Janus kinase 2 (JAK2), SH2-domain containing tyrosine phosphatase- (SHP-1), phosphospecific SHP-2, and signal transducer and activators of transcription (STAT), respectively. Transforming growth factor-β fibronectin in the culture medium of GMC was detectedby ELISA. Results: The phosphorylation levels of JAK2, STAT1, STAT3, andSHP-2 increased significantly, and SHP-1 phosphorylation was reduced in glom-eruli of diabetic rats. Treatment with fluvastatin reduced phosphorylation levels of JAK2, STAT1, STAT3, and SHP-2 in glomeruli of diabetic rats, but it had noeffect on the dephosphorylation of SHP-1. The exposure of GMC to 30 mmol / L glucose caused the activation of JAK2, STAT1, STAT3, and SHP-2. It upregulated TGF- β1 expression and increased protein synthesis of fibronectin.These highglucose-induced changes were suppressed by fluvastatin, as well as AG490, aJAK2 inhibitor. Conflusion: The regulation of the phosphorylation of JAK / STATby fluvastatin may be responsible for its renal protective effects on diabeticnephropathy.