Various surface modifications of iron oxide magnetic nanoparticles (IOMNs) can improve their stability and long-term retention time ， expanding applications of biomedical fields. However， whether the long-term retention of IOMNs coated with different surface modifications has toxic effects remains poorly understood. Here， the toxicity of IOMNs modified with polyethylene glycol (PEG)， bovine serum albumin (BSA)， and carboxyl group (COOH)， forming PEG-IOMNs， BSA-IOMNs， and COOH-IOMNs， respectively， were evaluated in the rats. The high accumulation of PEG-IOMNs and COOH-IOMNs both in the liver and lung， and the high accumulation BSA-IOMNs in blood after 24 day recovery were observed by elemental content analysis. Except individual neutrophils in the local portal area， PEG-IOMNs can also induce cytoplasmic vacuolisation in partial liver cells by histopathological examination. Furthermore， the results of RT-qPCR showed that PEG-IOMNs， BSA-IOMNs， and COOH-IOMNs can change the transcript levels of most genes related to iron homeostasis， mitochondria apoptosis， inflammatory response， but <2-fold alteration. COOH-IOMNs seemed to induce normal cell apoptosis more easily than BSA-IOMNs and PEG-IOMNs. In conclusion， BSA-IOMNs had longer-term retention time in blood. IOMNs coated with PEG and BSA can still induce side effects on the liver.