Aim To explore changes of gut microbiota in experimental model rats with hyperuricemia-induced mild cognitive impairment. Methods The experimental rats were provided with a diet containing 2% W/W uric acid (UA) and 2% W/W oxonic acid for period ranging from 1 day to 12 weeks. Morris water maze, blood biochemical indexes and other auxiliary models were used to evaluate the experimental animal model. Changes of gut microbiota were studied by 16S rDNA high-throughput sequencing. Results Compared with control group, the amount of UA of rats was significantly elevated. In addition, the rats showed significantly reduced spatial learning and memory in an escape latency and probe trial. The diversity of gut microbiota in model rats changed, and the relative abundances of 14 species of gut microbiota changed markedly. The abundance of Butyrivibrio, Erysipelotrichia, Erysipelotrichales, Erysipelotrichaceae, Erysipelatoclostridium, Lachnoclostridium 5, Anaeroplasmatales, Anaeroplasmataceae and Anaeroplasma in model mice increased, while that of Dorea, RuminococcaceaeUCG_005, Butyricicoccus, Tyzzerella 3 and Parasutterella decreased. Conclusions The continuous increase of UA can regulate gut microbiota, and the imbalance of gut microbiota is closely related to the development of mild cognitive impairment, which may be one of the mechanisms of hyperuricemia-induced mild cognitive impairment.