S-allyl-glutathione (SAG) is one of the metabolites of diallyl sulfide (DAS), a component of garlic. DAS has shown preventative effects on carcinogenesis in animal models. However, whether synthetic SAG can improve liver fibrosis has not been investigated. We examined the potential preventive effects of SAG on acute and chronic models of liver fibrosis by chronic carbon tetrachloride (CCl₄) administration. SAG inhibited liver fibrogenesis induced by CCl₄ in a dose-dependent manner and reduced heat shock protein 47 (HSP47), a collagen-specific chaperone and other fibrosis markers. In fibrosis regression models, either after CCl₄ administration for 9 weeks or dimethyl nitrosamine (DMN) for 6 weeks, SAG markedly accelerated fibrolysis in both models. In the regression stage of DMN-treated liver, SAG normalized the ratio of M2-phenotype (expression of mannose receptor) in Kupffer cells (KCs). Consistent with these results, the culture supernatants of SAG-treated M2-phenotype KCs inhibited COL1A1 mRNA expression in primary culture-activated rat hepatic stellate cells (HSCs). However, SAG did not directly inhibit HSCs activation. In acute model of CCl4 single injection, SAG inhibited hepatic injury dose-dependently in consistent with the inhibiting inflammatory KCs activation. These findings suggested that SAG could improve fibrogenic and fibrolysis cascade via the regulation of excess activated and polarized KCs. SAG may also serve as a preventive and therapeutic agent in fibrosis of other organs for which current clinical therapy is unavailable.