Aim To explore the effects and mechanism of ApoAⅠ on TNF-α expression in macrophages and plasma TNF-α levels from atherosclerotic mice. Methods Male ApoE-/- mice were fed with high cholesterol diet for 12 weeks and then randomly divided into control group, ApoAⅠ group and ApoAⅠ+AG490(a specific JAK2 inhibitor)group； each group were separately received treatment with PBS, ApoAⅠ (40 μg/g), ApoAⅠ (40 μg/g)+AG490(4 μg/g) on the third and the first day before sacrifice, 12 h before sacrifice all groups were administered with LPS via intraperitoneal injection, TNF-α levels in plasma were measured by ELISA. THP-1 macrophage-derived foam cells were randomly divided into control group , ApoAⅠ(10 mg/L)group and ApoAⅠ(10 mg/L)+AG490(25 μmol/L) group; all groups incubated with LPS (10 μg/L). TNF-α level in supernate were measured by ELISA and TNF-α mRNA expression were examined by RT-PCR. Results Compared with the control group, ApoAⅠ can significantly decrease TNF-α levels in mice plasma, after administered with AG490 ApoAⅠ-inhibition of TNF-α secretion induced by LPS markedly weakened(P<0.05). In vitro study demonstrated ApoAⅠ can inhibit TNF-α transcription and expression induced by LPS(P<0.01), AG490 abrogated the anti-inflammatory effect of ApoAⅠ(P<0.05). Conclusion ApoAⅠ inhibited TNF-α transcription and expression through JAK2/STAT3 signaling pathway.