The aim of the present study was to elucidate the long-term effect of epalrestat, an aldose reductase inhibitor (ARI), on renal function in patients with type 2 diabetes mellitus showing microalbuminuria. Patients were allocated to two groups (cases and controls) matched for age, BMI, and the extent of urinary albumin excretion (UAE). Thirty-five type 2 diabetic patients presenting microalbuminuria were included in this study: cases were treated with epalrestat (150 mg/day) for 5 years. No significant changes were found in blood pressure, HbA1c, and total cholesterol in either group during the observation period. In the control group, UAE increased significantly (P<.01) from 82+/-12 mg/g Cr at the baseline to 301+/-111 mg/g Cr at the end of the study, while UAE remained unchanged, 81+/-15 mg/g Cr at the baseline and 87+/-19 mg/g Cr at the end of the study, in the epalrestat-treated group. Reciprocal creatinine measured by an enzyme assay decreased significantly (P<.01) in both groups; however, the reduction rate in the epalrestat-treated group was significantly (P<.05) smaller than that in the control group. These results suggest the potential usefulness of ARIs in preventing the progression of incipient diabetic nephropathy in patients with type 2 diabetes mellitus.