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Colon cancer is one of the most common cancer in the world. Recently, natural products were used widely as complementer therapy for colon cancer. Previous study reported Nigella sativa has in vitro chemopreventive activity. This study aimed to observe the effect of cloroform extract of Nigella sativa seed (NSS) on rat colon cell after initiation of 7,12-dimethylbenz [a] anthracene. An experimental study design was set up with post only control group design using rats. Rats were divided into five groups, 12 rats in each group: Group I, the control group was given DMBA orally 20 mg/kgBW twice a week for five weeks, group V is the solvent control group was given corn oil. The other three groups were given DMBA + NSS, at the dosage of 250 mg/kgBW, 500 mg/kgBW and 750 mg/kgBW. NSS extract was dissolved in corn oil and administered daily per oral during the next two weeks before and during the initiation of DMBA. At the end of the experiment (16 week) all rats were sacrificed. Observations of colonic cell proliferation was performed using hematoxylin and eosin staining (H&E) and AgNOR. Data were analyzed using one-way ANOVA, followed by Tukey HSD. H&E staining showed that necrosis activity was lower in treated groups compared to DMBA group. AgNOR staining showed mAgNOR was significantly decrease following the increasing dose of NSS (250 mg/kgBW, 500 mg/kgBW and 750 mg/kgBW) were subsequently 1.62 ± 0.086, 1. 60 ± 0.101 and 1.39 ± 0.049 (p<0.05). The results showed that NNS reduce the damage of colon cells and inhibit colon cell proliferation in DMBA induced rats. This study indicated that Nigella sativa can be developed into chemopreventive agent for colon cancer.