The companion animal marker is growth to response the trend of fewer children and more elderly society in Taiwan, therefore the companion animal healthcare product development is expected. In this study, a liposome (SH-Lip.) was prepared by extracting phospholipids from shrimp head which is the by-products from seafood processing wastes. We were validated the immune regulation effects on canine macrophage cell line (DH82), mouse peritoneal macrophage cell line (RAW264.7) and the primary cell culture from canine peripheral blood mononuclear cell (canine-PBMC). The SH-Lip particle size was 129.2 nm approximately, and the potential on outer membrane was -31.7 mV. The cell viabilities were no significant affected, when co-cultured with below 1 mg/mL of SH-Lip. on LPS induced DH82 cell. On the lipopolysaccharide and interferon-g (LPS/IFN-g) costimulated DH82 cell inflammatory cell based assay, the anti-inflammatory gene expressions were up-regulated when the cell co-cultured with 0.037~1 mg/mL of SH-Lip., including TGF-b and IL-10. The pro-inflammatory cytokines such as IL-1b, IL-6, IL-12 and the monocyte chemoattractant protein-1 (MCP-1) in the supernatants were inversely significant downregulated, when the cell co-cultured with 0.11~1 mg/mL of SH-Lip. (P<0.05). Furthermore, the cytokines IL-6, IL-10, IL-12 and TNF-a secretions also markedly decreased (P<0.05) on LPS induced canine-PBMC cell, when the cell co-treated with 0.11~1 mg/mL of SH-Lip. On the other hands, the polarization of cell surface markers CD86 (M1) and CD206 (M2) were also analysis by flow cytometry. The results showed that M1/M2 ratio on the LPS induced RAW264.7 polarization is increase from 0.41 to 0.77, and the ratio is reduced to 0.58~0.45 when the cell co-cultured with 0.037~1 mg/mL of SH-Lip., seemed the co-culture SH-Lip help balance of M1/M2 ratio.Those results preliminarily showed that SH-Lip. should have the immunological activity for regulating DH82, canine-PBMC and RAW264.7 cells. SH-Lip. might be applied to the development of companion animal skin health products in the future.