Background: Cancer is a multistep process that develops very rapidly after its onset. Previous studies have confirmed antitumor effects of curcumin (1,7-bis (4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione; diferuloylmethane) that can potentially prevent colon cancer development with low side-effects. Different methods have been performed to increase the efficiency and effectiveness of curcumin among which dendrosome, a nanoparticle created by Sarbolouki et al. was used in this study. The present study was undertaken to evaluate the effects of dendrosomal curcumin on rat colon cancer. Methods: In this study which was performed in Cancer Research Center of Tehran University of Medical Sciences in 2010 year, forty rats were equally divided into control, curcumin and curcumin-dendrosome groups. Animals received azoxymethane (15 mg/kg s.c.), a carcinogen, once a week for two weeks. Curcumin (0.2%) and curcumin-dendrosome were administered to the respective animals 2 weeks before the first and 14 weeks after the last azoxymethane injections. Eventually, colorectal specimens from tumoral and adjacent non-tumoral mucosal tissues were fixed in 10% formaldehyde, and passaged and embedded in paraffin. Histopathological and immunohistochemical studies were performed on the specimens. Results: The mean number of lesions, nuclear/cytoplasmic ratio, epithelial stratification, loss of nuclear polarity, goblet depletion, structural abnormality and beta-catenin expression were higher in the control group compared to curcumin and curcumin-dendrosome groups. These parameters had significantly decreased in the dendrosomal curcumin group (P<0.05). Conclusion: The present study shows that dendrosome can be used as a suitable nanoparticle to increase curcumin efficiency in the prevention or treatment of colon cancer.