Two types of nanosized titanium dioxide, anatase (anTiO2) and rutile (rnTiO2), are widely used in industry,commercial products and biosystems. TiO2hasbeen evaluated as a Group 2B carcinogen. Previous reportsindicated that anTiO2 is less toxic than rnTiO2, however, under ultraviolet irradiation anTiO2 is more toxic thanrnTiO2 in vitro because of differences in their crystal structures. In the present study, we compared the in vivoand in vitro toxic effects induced by anTiO2 and rnTiO2. Female SD rats were treated with 500 mg/ml of anTiO2or rnTiO2 suspensions by intra-pulmonary spraying 8 times over a two week period. In the lung, treatment withanTiO2 or rnTiO2 increased alveolar macrophage numbers and levels of 8-hydroxydeoxyguanosine (8-OHdG);these increases tended to be lower in the anTiO2 treated group compared to the rnTiO2 treated group. Expressionof MIP1a mRNA and protein in lung tissues treated with anTiO2 and rnTiO2 was also significantly up-regulated,with MIP1a mRNA and protein expression significantly lower in the anTiO2 group than in the rnTiO2 group.In cell culture of primary alveolar macrophages (PAM) treated with anTiO2 and rnTiO2, expression of MIP1amRNA in the PAM and protein in the culture media was significantly higher than in control cultures. Similarlyto the in vivo results, MIP1a mRNA and protein expression was significantly lower in the anTiO2 treated culturescompared to the rnTiO2 treated cultures. Furthermore, conditioned cell culture media from PAM cultures treatedwith anTiO2 had less effect on A549 cell proliferation compared to conditioned media from cultures treatedwith rnTiO2. However, no significant difference was found in the toxicological effects on cell viability of ultraviolet irradiated anTiO2 and rnTiO2. In conclusion, our results indicate that anTiO2 is less potent in induction ofalveolar macrophage infiltration, 8-OHdG and MIP1a expression in the lung, and growth stimulation of A549cells in vitro than rnTiO2.