Objective: To study the in vivo pharmacological effects and antipsychotic activity of pimavanserin, a 5-HT2A receptor inverse agonists. Methods: The in vivo pharmacological effects and antipsychotic activity of pimavanserin were evaluated by DOI induced head shaking model in mice, DOI induced prepulse inhibition (PPI) injury model in rats and MPTP（1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine）+MK-801 {(+)-5-methyl-10,11- dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate)} induced parkinson′s disease psychosis (PDP ) model in mice. Results: Pimavanserin (0.1, 0.3, 1 and 3 mgkg-1) significantlyinhibited DOI-induced head shaking behavior in mice (P < 0.05 or P < 0.001), and the ED50 of pimavanserin inhibited head shaking behavior in mice was 0.20 mgkg-1. Pimavanserin 3 and 10 mgkg-1 could significantly reverse DOI induced PPI injury in rats (P < 0.05 or 0.01), but had no significant effect on PPI in normal rats at this dose. At 3 and 10 mgkg-1, pimavanserin significantly reduced the hyperactivity behavior induced by MK-801 in PD mice (P < 0.05), and the ED50 of pimavanserin in this PDP model was 2.86 mgkg-1. Conclusion: Pimavanserin can reverse DOI induced PPI injury in rats by blocking the function of 5-HT2A receptor in the brain, and has a significant improvement effect on MPTP+MK-801 induced PDP model in mice.