Neuroinflammation and apoptosis in the dopaminergic neurons of substantia nigra play an important role in the pathogenesis of experimental and clinical Parkinson's disease (PD). This study focused on the possible anti-inflammatory and anti-apoptotic effects of theaflavin (TF), a black tea polyphenol against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in mice. C57BL/6 male mice were treated with 10 doses of MPTP (25 mg/kg, s.c.) and probenecid (250 mg/kg, i.p.) for 3.5 days interval. TF (10 mg/kg) was administered 1 h prior to the administration of MPTP for 35 days of experimental period. MPTP/p treatment upregulates the release of interleukin-1beta, IL-6, tumor necrosis factor-alpha, IL-10, glial fibrillary acidic protein and Bax, and downregulates anti-apoptotic marker Bcl-2. Oral treatment of black tea polyphenol TF significantly attenuates MPTP-induced neuroinflammation as well as apoptosis. Behavioral studies (catalepsy and akinesia) were carried out to confirm these molecular studies. The results demonstrate that TF mediated its neuroprotection against chronic MPTP-induced toxicity through the involvement of multiple molecular events. It was concluded that TF may provide a precious therapeutic strategy for the treatment of progressive neurodegenerative disease such as PD in future.