In the present study, nanostructured lipid carriers (NLCs) with three different lipid combinations (solid lipid:liquid lipid) were prepared through emulsification and ultrasonication using a Box-Behnken design. From the design, the best lipid combination was glyceryl monostearate and oleic acid, which gives particle of smaller size (223.73 ± 43.39 nm) with high drug entrapment efficiency (78.65 ± 2.2%). In vitro release studies show that 84.60 ± 5.66% of drug was released in 24 h. In vivo studies revealed that drug absorption occurs through lymphatic pathway as only 5.008 ± 0.011 μg/ml of peak plasma concentration was achieved in blood plasma in presence of chylomicron inhibitor. The peak plasma concentration (Cmax) for silymarin loaded NLC was found to be 25.565 ± 0.969 μg/ml as compared to silymarin suspension whose Cmax was found to be 14.050 ± 0.552 μg/ml, this confirms 2-fold increase in relative bioavailability. In vivo studies revealed that 19.268 ± 1.29 μg of drug reaches to liver in 2 h whereas negligible drug concentration reported in other organs. It was concluded that drug loaded NLCs was beneficial for targeting liver or other lymphatic disorders through lymphatic transport pathway. Finally, the main purpose of modifying lymphatic transport system was successfully achieved through NLCs.