We have established tumor-resected mouse as a model animal to analyze the mechanism underlying the depression lasting after cancer remission. Our previous data showed that tumor-resected mouse has decreased sociability and morphological changes in hippocampal microglia on day 4 after tumor resection. Here, we aimed to elucidate whether the hippocampal microglia involved in abnormal sociability in tumor-resected mice. Male BALB/c mice were intradermally inoculated 1×10⁷ cells of colon 26 into their abdomen, and surgically resected formatted tumor on day 3 after tumor inoculation. Either fluoxetine (10 mg/kg), minocycline (50 mg/kg) or vehicle was orally injected for 14 days after tumor resection. We performed the social interaction test and preparation of the brain slices for immunohistochemical analyses on day 14 after tumor resection. On day 14 after tumor resection, tumor-resected mice had the hippocampal Iba1-positive cells with shortened processes, which is a morphological change observed in microglial cells. Fluoxetine or minocycline was effective in abolishing both abnormal sociability and the morphological change in the hippocampal Iba1-positive cells in tumor-resected mice.  These findings suggest the possibility that morphological and functional changes in the hippocampal microglia is involved in decreased sociability in tumor-resected mice.