The aim of this study was to assess the feasibility of solid lipid nanoparticles (SLN) to enhance the oral bioavailability of praziquantel (PZQ). SLN loaded with PZQ were produced by ultrasound technique. The characteristics of PZQ-SLN were studied in detail. The concentration of PZQ in plasma was determined using reversed-phase high-performance liquid chromatography after oral administration of PZQ-SLN and control PZQ tablets (PZQ-TAB) in rats respectively. The results showed that PZQ-SLN had an average diameter 110 nm with Zeta potential of -66.3 mV. The encapsulation efficiency of PZQ was about 80%. In vitro drug release fitted the Weibull distribution equation. There were two peaks in the PZQ concentration-time curves in plasma after oral administration of PZQ-SLN. The first peak might be caused by free drug and that adsorbed onto the surface of PZQ-SLN. The second peak was indicative of gut uptake of PZQ-SLN. The AUC(0-infinity) value of PZQ after oral administration of SLN was 4.1 fold higher than that obtained with the PZQ-TAB. The MRT of PZQ-SLN was also significantly enhanced, resulting in an about twofold increase compared with PZQ-TAB. Thus, the oral bioavailability of PZQ-SLN increased significantly compared to PZQ-TAB, and the results indicate that SLN can be a promising drug carrier for PZQ.