Chronic kidney disease is a worldwide health problem. Type II diabetes mellitus is now a major cause of end stage renal disease. The effect of diabetes mellitus through the dysregulation of the innate immunity results in increased tumor necrosis factor-alpha. This can lead to an increasing protein trafficking through the glomerular capillary, which can have an intrinsic renal toxicity. Seventy-four patients with type II diabetes mellitus with overt proteinuria were included in the study. They were randomly assigned to two groups of 37 patients (group 1: captopril 25 mg three times a day, group 2: captopril 25 mg and pentoxifylline 400 mg each three times per day). In the course of the study, two patients were excluded from each group. Daily urinary protein excretion was assessed at baseline and at two and six months. The reduction of urinary protein to creatinine clearance ratio in group 2 was 15.16 points more than in group 1 from baseline to the end of the study (p = 0.001). The difference in reduction only started after two months of pentoxifylline use. The differences in HbA1c and duration of diabetes mellitus at baseline in the two groups had not adversely affected the outcome of the study. There was a modest decrease in systolic blood pressure in group 2 as well (p = 0.041). Combining an angiotensin-converting enzyme inhibitor and pentoxifylline can lead to a greater reduction in proteinuria.