Purpose: Athough an effective direct renin inhibitor, aliskiren (ALS) presents with a low bioavailability coupled with high drug cost. As nanoformulation may increase drug bioavailability, our laboratory developed an ALS-loaded poly(lactic-co-glycolic) acid nanoparticle (ALS-NP) formulation. As such, the influence of nanoformulation on drug pharmacokinetic parameters were examined in this study. Methods: Following a single oral dose of ALS (n=7; 30 mg/kg) or ALS-NP (n=7; ALS dose equivalent), rats underwent pharmacokinetic sampling (0, 0.5, 1, 2, 4, 6, 8, 12, and 24 hrs post-dose). Plasma samples were assayed using LCMS-IT-TOF (coefficient of variation of <5%). Pharmacokinetic parameters (half-life, t1/2; maximum plasma concentration, Cmax; time to reach Cmax, tmax; the area under the plasma concentration time curve from 0 to infinity, AUC0-∞; apparent volume of distribution, V/F; and oral clearance, CLoral) were calculated using WinNonlin and evaluated using Student’s t-test with statistical significance set at p<0.05. All values shown as mean±SD. Results: While t1/2 (p=0.0517) and tmax (p=0.0961) were not significantly altered, Cmax in the ALS-NP group (448.53±49.07 mg/L) was elevated compared to control (288.60±148.07 mg/L; p=0.0189). ALS-NP also presented with a 168% relative bioavailability compared to ALS with respective AUC0-∞values of2592.82±600.51 and 1538.40±678.17 hr.mg/L (p=0.0095). The V/F of ALS-NP (128.56±43.67 L/kg) was significantly reduced (p=0.0009) compared to ALS (540.33±245.57 L/kg). A significant reduction (p=0.0298) was also detected in CLoral (ALS-NP, 12.26±3.59 L/hr/kg vs. ALS, 23.44±11.45 L/hr/kg) Conclusion: This study indicates that ALS-NP can be used to improve bioavailability of the drug.