Objective: To investigate the influence of sirolimus on the disease progression of a rat model of autosomal dominant polycystic kidney disease (ADPKD) - Han : SPRD with chronic renal insufficiency. Methods: Twenty 6-month-old male ADPKD heterozygous (Cy/+) rats with chronic renal insufficiency were divided into 2 groups at random (n=10). Rats in experimental group received intragastric administration of sirolimus (0.2 mg · kg-1 · d-1) for 45 days and those in control group were bred routinely. The general state and renal function of rats were monitored throughout the treatment. The rats were sacrificed 45 days later and both kidneys were harvested, weighed; and the 2-kidney/ total body weight (2K/TBW) ratio was determined. Then the kidneys were subjected to immunohistochemistry examination and the numbers of cells positive of proliferating cell nuclear antigen (PCNA) were counted. Results: There was no death in the 2 groups and all rats gained weights, with no significant difference between the 2 groups, Blood urea nitrogen (BUN) increased progressively in both groups, with the increase in experimental group lower than that in the control group by 12.5 % on 45 days after administration (P<0.05). The 2-kidney-weight and 2K/TBW ratio in experimental group was lower by 11.8 % (P<0.05) and 7.1 % (P<0.01) than those in the control group, respectively. Renal enlargement and cystogenesis were inhibited by sirolimus, with the number of PCNA-positive cells per cyst being 0.23±0.11 in experimental group and 0.47±0.24 in the control group (P<0.05). Conclusion: Sirolimus can slow down the disease progression in Han: SPRD rats with ADPKD, even though they had been in a condition of renal insufficiency.