Objective To investigate the curative efficacy of epalrestat in combination with alprostadil injection in the treatment of early diabetic retinopathy (DR) and its effects on oxidative stress and inflammatory factors. Methods Eighty patients of early DR meeting the inclusion criteria were collected as research objects. According to random number table, those patients were randomly divided into the control group (40 cases with 76 eyes) and the observation group (40 cases with 74 eyes). Besides the conventional treatment, the control group was treated with alprostadil injection, while the observation group was treated with epalrestat in combination with alprostadil injection. The curative efficacy, levels of oxidative stress indices and inflammatory factors were compared. During the treatment, the adverse reactions were compared. Results After the appraisal, the observation group had a total therapeutic efficacy ratio of 95.0%, which was statistically higher than that of 80.0% in the control group (P < 0.05). After the treatment, in comparison with the control group, oxidative stress indices of malonaldehyde (MDA) was statistically lower (9.28 ± 2.04 vs 12.17 ± 2.13 nmol/ml, P <0.05) and superoxide dismutase (SOD), total antioxidant capacity (TAC) were statistically higher (93.18 ± 10.02 vs 82.53 ± 9.27 U/ml, 20.52 ± 3.84 vs 18.28 ± 3.55 U/ml, P <0.05) in the observation group. As to inflammatory factors, the observation group showed statistically lower levels of TNF-α, IL-2 (11.51 ± 2.12 vs 16.36 ± 2.45 ng/L, 0.48 ± 12.14 vs 82.56 ± 11.37 ng/L, P < 0.05) and statistically higher level of IL-10 (64.52 ± 8.97 vs 57.38±8.47 pg/ml, P < 0.05) than those in the control group after the treatment. During the treatment, there was no case of severe adverse reactions. Conclusions Epalrestat in combination with alprostadil injection is effective for early DR, which can significantly increase curative efficacy, alleviate oxidative stress and inflammatory reaction with minor adverse reactions.