Diabetic nephropathy (DN) is one of the complex complications of diabetes mellitus (DM). The present study has been designed to examine the possible protective effects of the transient receptor potential canonical type 1 (TRPC1) on DN. After administrated with TRPC1, the levels of blood glucose, urine protein, blood urea nitrogen (BUN) and serum creatinine (SCr) in DN rats were significantly decreased compared with the model rats. In addition, morphological studies demonstrated that TRPC1 attenuated mesangial expansion and capillary basement membrane thickening as well as glomerular structure. The treatment of TRPC1 reduced the inflammatory cytokines including transforming growth factor-β1 (TGF-β1) and nuclear factor kappa B (NF-κB) though the immunohistochemical analysis. In addition, related-mRNA and proteins of NF-κB signal pathway were investigated to determine the protective molecular mechanism of TRPC1 on the DN. The results presented here suggest that the protective mechanism of TRPC1 may be attributed partly to decreased production of pro-inflammatory cytokines via the inhibition of NF-κB signaling pathway.