Objective: To observe the toxic effects of cockle shell-derived calcium carbonate nanoparticles (CCNPs) on female SD rats, and to preliminarily explore the safe dose of CCNPs. Methods: Healthy female SD rats were randomly divided into 4 groups: control group, CCNPs low dose group (30mg/kg/d), CCNPs middle dose group (60mg/kg/d) and CCNPs high dose group (120mg/kg/d). The rats in 3 CCNPs groups were given different dose of CCNPs by tail vein injection for 14 days continuously;The rats in control group were given normal saline by tail vein for 14 days.The survival rate, toxic effects, weight changes of rats were recorded; HE stain was used to observe the pathological changes of main organs. Results: At the end of the experiment, the survival rate of rats was respectively 100%, 66.67% (4/6) and 50.00%(3/6) in CCNPs low, middle and high dose group. There was no significant difference in body weight between CCNPs low, middle dose group and control group (P>0.05); the body weight of rats in CCNPs high dose group were obviously lower than control group (P<0.05). Histopathological observation showed that the pathological changes of liver, spleen, lung, heart and kidney in CCNPs low dose group were mild or no obvious pathological changes were observed, while the pathological changes of aboving organs in middle and high dose group were more serious. Conclusions: Intravenous administration of low dose CCNPs do not cause sever acute toxicity of female SD rats, so the safe dose of CCNPs is less than or equal to 30 mg/kg.