An essential research tool for studying colorectal cancer (CRC) is the use of 1, 2-dimethylhydrazine (DMH) as an animal model of colorectal carcinogenesis. Niclosamide (Nic), an oral anthelmintic drug, has been identified as a possible anticancer agent. The purpose of this research was to determine the potential antineoplastic effect of Nic on induced colorectal carcinogenesis. Five groups from thirty-five albino rats were created. Group I was given a vehicle for four weeks. Group II was administered Nic I/P at a dose of 20 mg/kg b.w. daily for four weeks. Group III was administered DMH S/C at a dose of 20 mg/kg b.w. twice weekly for four weeks. Group IV received DMH in the same manner as Group III, and following a week from the last DMH injection, they were given daily doses of 20 mg/kg b.w. of Nic I/P until the experiment concluded. Group V received for four weeks both DMH S/C at a dose of 20 mg/kg b.w. twice weekly and Nic I/P at a dose of 20 mg/kg b.w. daily. Upon completion of the experiment, which lasted 12 weeks, rats were sacrificed for sampling. Colons of rats in all groups were collected for aberrant crypt foci (ACF) counting using 0.2% methylene blue. Then tissue specimens were taken for histopathological examination. According to the topographical features of colon preneoplastic lesions, we found that group III had more ACF count and crypt multiplicity, whereas groups IV and V had a significantly lower number. Microscopically, rats receiving DMH exhibited moderate to severe dysplastic changes. These changes were significantly decreased in both Nic-treated groups, however, Group V showed the best improvement. These results indicated the obvious protective effect of Nic against ACF progression.