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Objective To prepare Nimodipine/Tetramethylpyrazine-loaded ploy(D,L-lactide-co-glycolide) nanoparticles (NMD/TMP-PLGA-NPs) and investigate their in vitro release behavior and in vivo pharmacokinetics.Methods NMD/TMP-PLGA-NPs were prepared by emulsion solvent precipitation method with PLGA as a carrier material; morphology of NPs was observed by transmission electron microscope; mean particle size and Zeta potential were estimated by laser particle size analyzer; entrapment efficiency and drug loading were investigated by ultracentrifugation; drug release behavior in vitro was studied by dialysis; pharmacokinetics behavior of NMD/TMP-PLGA-NPs were studied in comparison with NMD-Suspension, NMD/TMP-Suspension and NMD-PLGA-NPs after vein injection.Results The morphology of NMD/TMP-PLGA-NPs was spherical, the mean particle size, particle size distribution of NPs were (631.60 ± 3.20) nm, (-29.25 ± 1.87) mV, respectively.The entrapment efficiency and drug loading of NMD were (76.25 ± 1.18) %, (1.24 ± 0.01) %, those of TMP were (39.30 ± 1.00) %, (6.34 ± 0.11) %.The profiles of release in vitro had the features of sustained release.The concentration-time curve was fitted to two-compartment model, t1/2β were (0.8821 ± 0.0889)、(1.2233±0.1572)、 (1.7260±0.0891)、 (1.4636±0.0454) h, CLwere (4.0108±0.1404)、 (4.699 ± 0.0389)、 (1.1092 ± 0.0488)、 (1.5867 ± 0.0761) h/L, AUC0→t were (109.7913 ± 3.7878)、 (93.6363 ± 0.7744)、 (397.2019 ± 17.6517)、 (277.7338 ± 13.3299) μg·h/L, respectively.Conclusion NMD/TMP-PLGA-NPs were prepared successfully and showed sustained-release characteristics in vitro and in vivo, the pharmacokinetic behavior of NMD were markedly improved by TMP no matter in NMD/TMP-suspension or NMD/TMP-PLGA-NPs.