Genistein is the most bioactive isoflavone of soybean. It has been known with its effects as estrogen, antiestrogen, cancer inhibitor, and immune regulator. In this study, we investigated the effects of genistein on chemically induced soft tissue sarcoma in the rats. Forty-five male Wistar albino rats were randomly allocated to 3 experimental groups containing 15 rats in each. (i) Control: Standard control animals (no treatment). (ii) DMBA: These rats received 7,12-dimethylbenz[a]anthracene (DMBA) (50 mg/kg body weight of DMBA dissolved in sesame oil) i.p. injected to develop fibroid tumor. (iii) DMBA+Genistein: This group received DMBA i.p. similarly as DMBA group to develop fibroid tumor as well as supplemented with genistein (400 mg/kg diet) for 20 weeks of the study duration. Genistein supplementation decreased the incidence of fibroid tumors (P<0.01). The tumors found in DMBA+Genistein group were smaller than those found in DMBA group (P<0.001). Serum MDA (P<0.01), 8-isoprostane and HAE levels were lower in DMBA+Genistein group than DMBA group (P<0.05). The concentrations of serum 8-OHdG, which is a marker of oxidative damage, in the groups were lowered in DMBA+Genistein group compared to DMBA group (P<0.05). These results showed that genistein supplementation is able to inhibit the development of DMBA-induced soft tissue sarcomas in rats.