Microglial cell is a macrophage that resides in brain. However, overactive microglial cells may result in brain neuron damage or inflammation. Recent studies show that the initiation of anti-inflammatory is triggered by macrophage engulfed apoptotic bodies. In this study, the liposome (SQ-liposome) was made from phospholipids extracted from squid skin, and used to mimic apoptotic body. The anti-inflammatory effects of SQ-liposome were then evaluated on the lipopolysaccharide (LPS) induced mouse microglial cell line (BV-2). The major phospholipid constituents in the squid skin extract was including 46.2% of phosphatidylcholine, 18.4% of phosphatidylethanolamine, 7.7% of phosphatidylserine, 3.5% of phosphatidylinositol, 4.9% of Lysophosphatidylcholine, and 19.3% of other phospholipids in HPLC-UV analysis. An approximately 100 nm of SQ-liposome was prepared by ultrasonication. There was no cytotoxicity to BV-2 as the concentration of SQ-liposome was less than 2.5 mg/ml after microglial cells engulfed SQ-liposome. The LPS induced pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), were significantly suppressed (p < 0.05) by pretreated 0.83~2.5mg/ml SQ liposome. Oppositely, the anti-inflammatory cytokines transforming growth factor-beta (TGF-β) and interleukin-10 (IL-10) secretion were enhanced (p < 0.05). The results suggested that SQ-liposome possess anti-inflammatory properties on BV-2 and may be a good strategy for against neuro-inflammatory disease.