We have previously reported that nicotine (Nic) facilitates object recognition memory (ORM) encoding via activation of excitatory neurons in the medial prefrontal cortex (mPFC) in mice. In this study, we investigated whether Nic also facilitates ORM retrieval using the novel object recognition test (NOR). Male C57BL/6J mice (7 – 12 weeks) received Nic before the test session, which was performed 24 hours after the training session of the NOR. Systemic administration (0.1 mg/kg; s.c.), but not intra-mPFC infusion (0.3 μg/side), of Nic enhanced ORM, suggesting that Nic facilitates ORM retrieval by acting on brain regions other than the mPFC. However, suppression of mPFC neuronal activity with inhibitory DREADD hM4Di, which was specifically expressed in excitatory neurons using an AAV vector, significantly inhibited the systemic Nic-induced facilitation of ORM retrieval. Moreover, activation of mPFC excitatory neurons with excitatory DREADD hM3Dq significantly facilitated retrieval of ORM. These data suggest that Nic facilitates ORM retrieval through the indirect activation of mPFC excitatory neurons.