Objective To study the preparation of Oenothera biennis oil solid lipid nanoparticle (GLA-SLN) and its effect on reducing blood lipid in hyperlipemia mice model.Methods The solid lipid nanoparticles were prepared by microemulsion technique.The optimum condition was performed based on the orthogonal design test, The mice were all administered intraperitoneally egg yolk emulsion to cause hyperlipidemia model, and contends of cholesterol(TC), triglyceride(TG) and high density lipoprotein(HDL-C) in serum were measured, and caparisoned with commercially available Oenothera biennis.L soft capsules.Results The diameter of GLA-SLN was 44.43±0.08 nm, the Zeta potential was 64.72 ± 1.24 mV and the encapsulation of efficiency was(89.89 ± 0.71) %;Normal-dose, middle-dose and high-dose of GLA-SLN reduced the levels of TC and TG in serum of hyperlipidemia mice,and increased HDL-C levels, which was better than Oenothera biennis.L soft capsules.Conclusion GLA-SLN has significant therapeutic effect by intraperitoneal injection of egg yolk emulsion in mice to induced acute hyperlipidemia..