Objective To investigate the effect of canagliflozin (sodium-glucose cotransporter 2 inhibitor, SGLT-2i) on the ratio of urine albumin-to-creatinine ratio(UACR) and urine podocyte-related protein nephrin in early diabetic nephropathy. Methods From January 2018 to July 2019, 116 patients with early diabetic nephropathy who were hospitalized in the Department of Endocrinology, Southern University of Science and Technology Hospital were enrolled. They were divided into canagliflozin group and control group with 1∶1 random number method. One hundred and five(90.5%) patients completed all studies, 51 were in the canagliflozin group and 54 were in the control group. The canagliflozin group was routinely given canagliflozin 100-300 mg/d, the control group received basal insulin and losartan potassium tablets 100 mg/d, and the patients in both groups were treated 24 weeks. The biochemical indicators of the patients were tested before treatment, 12-weeks and 24-weeks treatment. The UACR and the urine podocyte-associated protein nephrin before and after treatment were compared between groups and within groups. Results Compared with before treatment, both UACR and nephrin in the canagliflozin and the control groups improved after 12 weeks and 24 weeks treatment (P<0.05). Before treatment and after 12-weeks treatment, the UACR and nephrin indexes in canagliflozin and control groups didn’t show significant difference (P>0.05); while after 24-weeks treatment, these indexes in the canagliflozin group were significantly better than the control group(P<0.05). Conclusions Canagliflozin can continuously reduce the content of podocyte-associated protein nephrin in urine of early diabetic nephropathy. It is speculated that the renal protection of SGLT-2i drugs is independent of the effect of lowering the blood sugar.