Abstract: The solid lipid nanoparticle of cucurbitacin B was prepared by high pressure homogenization with the lipid of monoglyceride, the emulsifier of mixture of the soybean lecithin and poloxamer 188 (1∶1) .The parameters of the high pressure homogenization were optimized by response surface methodology with the homogenization pressure, lipid content and emulsifier content as the main factors, and the encapsulation efficiency as the response. The homogenization pressure was the key factor affecting the encapsulation efficiency of cucurbitacin B, followed by the lipid content and emulsifier content. When the homogenization pressure was 74.8 MPa, and the ratio of the lipid-emulsifier-cucurbitacin B was 12.6∶10.3∶1, the encapsulation efficiency of cucurbitacin B reached the maximum of 92.4%. The validation experiment showed that the relative deviation between real and theoretical value was only 1.62%.The regression model was reliable.