〔Abstract〕 Objective　To investigate whether fullerene C60 administered by intratracheal spraying promotes N-bis （2-hydroxypropyl） nitrosamine （DHPN） induced-lung tumor development and the underlying mechanisms.Methods　A rat lung tumor model was induced by the DHPN drinking water method. Eight-week-old male Fisher 344 rats were randomly divided into 5 groups （n = 15）： DHPN+Veh group （0.2% DHPN + vehicle solution）， DHPN+C60-L group （0.2% DHPN + 250 μg/mL C60）， DHPN+C60-H group （0.2% DHPN + 500 μg/mL C60）， DHPN group （0.2% DHPN）， and C60-H group （normal drinking water + 500 μg/mL C60）. 0.2% DHPN in drinking water was given to initiate carcinogenesis， and 2 weeks later， different concentrations of fullerene C60 were administered by intratracheal spraying every two weeks for a total of 20 times. Two weeks after the last spraying， the incidence， number and size of lung tumors were statistically analyzed. In another mechanism animal experiment， 8-week-old male Fisher rats were divided into two groups with 5 rats in each group： C60 group and the control vehicle group. 500 μg/mL C60 or the control vehicle intratracheally sprayed every two days for a total of 5 times. Six hours after the last spraying， the lungs were removed and used for observation of C60 distribution and for detection of SOD， 8-OHdG and cytokines in lung tissues. Results　No lung tumorigenesis was observed in the C60-H group； the incidence， number and size of lung tumors in the DHPN+C60-H group were significantly higher than those in the DHPN+Veh group （P<0. 05， P<0. 001， P<0. 05） and the DHPN group （P<0. 01， P<0. 001， P<0. 01）， re‑spectively. In additional animal experiments designed for mechanistic investigation， the levels of SOD and 8- OHdG in the experimental group were markedly elevated compared with the control group （both P<0. 001）， with statistically significant differences. Conclusion　Intratracheal nebulization of high-concentration fullerene C60 pro‑ moted DHPN-induced lung tumorigenesis； C60 led to an increase in reactive oxygen species （ROS） production， thereby elevating the potential for gene mutation. This may represent one of the mechanisms underlying C60-in‑ duced promotion of lung tumorigenesis.