Objective To establish the background database of non-proliferative spontaneous lesions of F344 rats for drug safety evaluation． Methods SPF F344 rats 336，male and female in half，8 months old，kept under the center barrier，were randomly divided into four groups，animals were killed32，64，64，176 at respectively 6，12，18 and 24 months time points． Tissues were examined under microscopic，and statistics 4 time points observed spontaneous animal disease type and disease incidence． Results Non-proliferative lesion consists of murine progressive cardiomyopathy，BALT，tubular lesions，and genital tissue degeneration such as reduction of ovarian cells or inhibition of spermatogenesis．Conclusions Under the condition of center barrier，the incidence of non-proliferative lesions of F344 rat increased． The present study enriched the existing F344 rat pathology background information，and laid the foundation for carrying out drug safety evaluation and research．