Objective: To investigate the effect of vitamin D3 on mild cognitive impairment in type 2 diabetic mice and explore its possible mechanism. Methods: Male db/db mice were randomly divided into 4 groups: the diabetes mellitus (DM) group, the low dose [250 IU/(kg·d)], medium dose [500 IU/ (kg·d)] and high dose [1 000 IU/(kg·d)] vitamin D3 intervention groups. The db/m mice were enrolled as the normal control group. The mice in vitamin D3 groups were gavaged with corresponding concentration of vitamin D3 in corn oil, and the mice in the normal control group and the DM group were gavaged with corn oil. After being fed for 16 weeks, fasting blood glucose of mice in each group was measured at the end of 0, 4, 8 and 16 weeks, and the new object recognition experiment was conducted at the end of 16 weeks. At the end of the experiment, the hippocampi and cortices of mice in each group were collected, and the concentration of 5-hydroxytryptamine (5-HT) and interleukin-18 (IL-18) in the hippocampal tissues of mice in each group were determined by enzyme linked immunosorbent assay (ELISA). Immunohistochemical staining was used to observe the expression of nucleotide binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) in the hippocampal tissues of the mice. Results: Compared with the normal control group, the fasting blood glucose of mice in DM group was significantly increased (P < 0.01). The exploration and discrimination index (DI) in the new object recognition experiment were significantly decreased (P < 0.05). The concentrations of 5-HT in the hippocampal tissues of mice were significantly decreased (P < 0.01). The concentrations of IL-18 in cortical tissues of mice were significantly increased (P < 0.01) and the positive expression of NLRP3 in the hippocampal tissues was higher. However, compared with the DM group, the fasting blood glucose of mice was significantly decreased in the medium and high dose vitamin D3 groups at the end of 8 and 16 weeks (P < 0.05 or P < 0.01). The exploration and DI of mice in the new object recognition experiment were significantly increased in high dose vitamin D3 group (P < 0.05). The concentrations of 5-HT in hippocampal tissues were significantly increased (P < 0.01) and the concentrations of IL-18 in cortical tissues were significantly decreased in the medium and high dose vitamin D3 groups (P < 0.01). The positive expression of NLRP3 in hippocampal tissues was reduced in all the vitamin D3 groups. Conclusion: Vitamin D3 might reduce the inflammatory response by inhibiting the activity of NLRP3, and thus ameliorating mild cognitive impairment in type 2 diabetic mice.