Objective To investigate the efficiency of alprostadil combined with conventional therapy on elderly type 2 diabetes mellitus (T2DM) patients complicated with chronic kidney disease (CKD). Methods A total of 90 elderly T2DM patients with CKD admitted in our hospital from February 2014 to February 2016 were recruited in this study. They were randomly divided into alprostadil group and control group (n=45). Conventional basic treatment was given to the patients of the 2 groups, and 10 μg/d alprostadil (once per day) was given to the alprostadil group by intravenous injection with 2 weeks as a course, for totally 3 courses. The indices of blood lipids, blood glucose, liver function and renal function were compared between the 2 groups. SPSS statistics 17.0 was used to analyze the data. The measurement data were expressed as mean±standard deviation ([AKx-D]±s), and Student’s t test was employed for the comparison between groups. Enumeration data were expressed as percentage, and inter-group comparison was carried out with Chi-square test. Results There were no significant differences in fasting plasma glucose (FPG), glycosylated hemoglobin A1c (HbA1c), triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), homocysteine (Hcy), blood β2-microglobulin (β2-MG), serum creatinine (SCr), and urinary albumin excretion rate (UAER) and estimated glomerular filtration rate (eGFR) between the 2 groups before treatment (P>0.05). After the treatment, the levels of TG, TC, LDL-C, Hcy and β2-MG and UAER were significantly lower in the alprostadil group than in the control group (P<0.05). No significant differences were observed in prothrombin time (PT), platelet (PLT) count, and activated partial thromboplastin time (APTT) between the 2 groups before and after treatment (P>0.05). There were no any differences in the incidences of adverse reaction (Chi-square=0.212, P=0.645). Conclusion Combination of alprostadil and conventional therapy can significantly reduce urinary protein levels and exert protective effect on renal function in elderly T2DM patients with CKD.