Introduction To investigate the reno-protective effect of beraprost sodium (BPS) in patients with diabetic nephropathy (DN).Methods We retrospectively analyzed patients with DN hospitalized in China-Japan Friendship Hospital from January 2015 to December 2021 who received combination of conventional treatment and BPS (120 ug/day) therapy. We selected patients with DN matched in age and estimated glomerular filtration rate (eGFR) as controls, who received only conventional therapy. Baseline information and clinical variables at each follow-up visit were collected from all patients. The changes of clinical variables were compared between the two groups before and after treatment.Results A total of 50 patients with DN met the inclusion and exclusion criteria, with 25 patients in each group. The baseline characteristics of the two groups have no significant difference (p > 0.05). Serum albumin levels after treatment were improved in both groups, but the improvement was statistically significant only in BPS group (35.5-39.8 g/l, p < 0.001). The eGFR worsened significantly in both groups (p = 0.009 and p = 0.001). However, the decline of eGFR was less in BPS group than that in control group (- 9.8 vs. - 16.7 ml/min/1.73 m(2), p = 0.037). In the subgroup analysis, 30 patients received 3-12 months treatment and 20 patients received more than 12 months treatment. During the 3-12 months treatment period, serum creatinine and eGFR in the control group were significantly worsened compared with those before treatment (p = 0.019 and p = 0.03), but in the BPS group they were relatively stable (p > 0.05). After more than 12 months treatment, although the serum creatinine and eGFR were significantly worsened in both groups (p < 0.05), the decline of eGFR was less in BPSgroup than that in control group (- 10.1 vs. - 25.9 ml/min/1.73 m(2), p = 0.045).Conclusions Combination of conventional treatment and BPS therapy delays the decline of eGFR in patients with DN in the long term.