Objective: This study is designed to observe the chronic toxicity after the administration of mulberry sea-buckthorn beverage concentrate for 3 months on rats and to predict the possible adverse effect and the potential toxicity target organs. Method: The rats (SPF level) were randomly divided into high-dose (20 mL/kg BW), middle-dose (10 mL/kg BW), low-dose (5 mL/kg BW) groups and negative control group (20 mL/kg BW of purified water) with 30 rats in each group. Each group was orally given mulberry sea-buckthorn beverage concentrate for 3 months and recovered by stop feeding samples for 2 weeks for a recovery observation. The rats’ general condition, the organ coefficient, the indexes of hematology and blood biochemistry and the histological changes of the main organs were determined. Result: The appearance and behavior of activity in rats showed no anomalies in all these groups and all the rats put on weight during this period. Comparing to the negative control group, no obvious differences were observed in the weekly weight and organ coefficient of each dose group. After 3 months of administration, HGB in both mulberry sea-buckthorn beverage concentrate low-dose group and high-dose group were increased. No significant differences were observed in the indexes of hematology after 2 weeks of recovery. CREA in low-dose, middle-dose and high-dose groups were significantly increased after 3 months of administration and it remained in the high level in middle-dose and high-dose group even after 2 weeks of recovery. No drug-related lesions were observed in the histological changes of major organs. Conclusion: The results show that long term use of mulberry concentrated sea-buckthorn beverage can lead to increased CREA, which suggested kidney toxicity. Although no obvious pathological change was found in kidney, we should pay attention to chronic kidney damage in the further research.