Background: The development of methods to alleviate radiation-induced health effects is important for the practical use of radiation therapy and for understanding the molecular mechanisms mediating these effects. Here, we examined the protective capability of N-acetylcysteine (NAC) on life-shortening effects induced by continuous low dose-rate gamma-ray exposure in mice. Materials and Methods: Female B6C3F1 mice were exposed to gamma-rays for 400 days at a dose rate of 20 mGy/day beginning at 8 weeks of age. Control unexposed mice and exposed mice were divided into two groups; the first was provided with regular water, and the second was administered 40 mM NAC during the exposure period. Results: Although NAC administration did not affect the life span of non-irradiated mice (p = 0.232), a 59-days life extension was observed in the exposed group (p = 0.0177). Moreover, radiation exposure and NAC treatment affected body weight. The reduction of body weight observed in NAC treated mice was associated with a reduction in water intake. Conclusion: Our data demonstrated that the life-shortening effects of chronic low dose-rate radiation exposure in mice were alleviated by NAC administration.