OBJECTIVE: To investigate the effects of dexmedetomidine (Dex) treatment administered at various times on acute lung injury (ALI). MATERIALS AND METHODS: Thirty Wistar rats were randomly divided into five groups (n = 6/group). Lipopolysaccharide (LPS) was intraperitoneally injected into the rats in the LPS, Dex1, Dex2, and Dex3 groups to induce ALI, while the control group (C) was left untreated. Rats in the Dexl group were intraperitoneally administered with 50 erg/kg Dex 30 minutes before modeling. Rats in the Dex2 group were injected with 25 mu g/kg Dex 30 minutes before modeling and two hours after. Rats in the Dex3 group received 50 mu g/kg Dex two hours after modeling. The animals in the C and LPS groups were given an equal volume of saline. The wet-to-dry (W/D) weight ratio of the rats' lungs was calculated, and pathological alterations in lung tissues were observed. The concentrations of inflammation-related factors and the expression of Janus kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3). and matrix metallopeptidase 9 (MMP9) were measured. RESULTS: The W/D ratio, expression of inflammatory factors, and expression of JAK1. STAT3, and MMP9 were significantly increased in the ALI rats (p < 0.05) compared with the C group. The level of anti-inflammatory factors in the Dex-treated groups was also significantly increased compared with the LPS group (p < 0.05). The concentration of anti-inflammatory factors in the Dex2 group was significantly higher than that recorded in the Dex1 and Dex3 groups (p < 0.05). CONCLUSIONS: Dex treatment administered at different times protects rats against LPS-induced ALI to varying degrees. The protective effects of Dex were most robust when administered both before and after LPS stimulation.