【Abstract】 Objective To explore the effect of epalrestat combined with alprostadil in the treatment of elderly patients with diabetic nephropathy. Methods A total of 97 elderly patients with diabetic nephropathy in Jigang Hospital of Jiyuan, Henan Province from July 2021 to July 2023 were selected as the research objects. The patients were divided into a prostaglandin group and a aldose reductase inhibition group by a lottery method. Forty-eight patients in the prostaglandin group were treated with alprostadil, and 49 patients in the aldose reductase inhibition group were treated with epalrestat combined with alprostadil. After 3 months, the renal function, microinflammatory state, renal interstitial artery hemodynamic parameters, and adverse reactions were compared between the two groups. Results After 3 months of treatment, the levels of serum creatinine(Scr) and bloud urea nitrogen(BUN) levels decreased compared to pre-treatment levels in both groups, and those in the aldose reductase inhibition group were lower than those in the prostaglandin group (P ＜ 0.05). After 3 months of treatment, the superoxide dismutase(SOD) and glutathione peroxidase(GSH-Px) levels in both groups increased compared to those before treatment, with the aldose reductase inhibition group showing higher levels than the prostaglandin group. The malondiald-ehyde(MDA) level decreased in both groups compared to that before treatment, and that in the aldose reductase inhibition group was lower than that in the prostaglandin group (P ＜ 0.05). After 3 months of treatment, the peak systolicflow velocity Vmax and end-diastolic flow velocity Vmin levels of the two groups increased compared to those before treatment, and the aldose reductase inhibition group showed higher levels than the prostaglandin group. The level of resistance index(RI) decreased in both groups compared to that before treatment, with that in the aldose reductase inhibition group lower than that in the prostaglandin group (P ＜ 0.05). There was no significant difference in the incidence of adverse reactions between the aldose reductase inhibition group (8.16%, 4/49) and the prostaglandin group (4.17%, 2/48) by Fisher exact test (P ＞0.05). Conclusions Epalrestat combined with alprostadil can regulate renal interstitial artery hemodynamic parameters, improve renal function, and regulate microinflammation in elderly patients with diabetic nephropathy with good safety.