This research was conducted to investigate the protective effect Polygonum minus leaves extract on the histopathological changes of kidney induced by mercuric chloride in mice (Mus musculus). Thirty male mice were divided into five groups and were administered via intragastric gavage with different treatments for 21 days. The treatment were C-(CMC Na 0.5% solution + aquadest), C+ (CMC Na 0.5% solution + 8 mg/kg bw of mercuric chloride), T1, T2, and T3 (200, 400, and 800 mg/kg bw of Polygonum minus leaves extract respectively + 8 mg/kg bw of mercuric chloride). The histopathological changes of kidney were examined by using Arshad Scoring method.Then the data was analysed using Kruskal Wallis and continued with Mann-Whitney test. The result showed Polygonum minus leaves extract could protect mice kidney from the damage effect of mercuric chloride. The best dose of Polygonum minus on this research was 400 mg/kg bw.