INTRODUCTION: Parkinson’s disease (PD) is a common neurodegenerative movement disorder. It is characterized by a progressive degeneration of dopaminergic substantia nigra neurons projecting to the striatum, as well as, by an accumulation of intraneuronal Lewy bodies containing misfolded a‑synuclein. Neurodegeneration is coincident with a decrease in dopamine, the dopamine transporter, and the dopamine metabolites levels in PD brain. Current therapeutic approaches for the treatment of PD are only symptomatic and do not block neuronal loss. Recently, an enormous amount of work has been conducted to identify molecules that could be used as neuroprotective agents. One of them is cystamine – the inhibitor of transglutaminases activity. Transglutaminases are involved in the formation of a-synuclein aggregates, therefore blocking of its activity may prevent the progression of PD. AIM(S): The aim of the present study was to examine the effects of cystamine on neurodegenerative processes in the murine model of PD. METHOD(S): Male 1‑year‑old C57Bl/10 Tar mice were used in this study. Cystamine was injected intraperitoneally for 14 days, beginning 13 days prior to 1‑methyl‑4‑phenyl‑1,2,3,6‑tetrahydropyridine (MPTP) intoxication. Changes in the mRNA level of inflammatory factors in striata were examined using Real‑Time PCR. Neurotransmitter levels in striata were evaluated by high‑performance liquid chromatography (HPLC). RESULTS: Our study demonstrated that chronic administration of cystamine before MPTP intoxication improved striatal levels of dopamine and its metabolites, as compared to MPTP‑treated groups. We also observed an inhibition of inflammatory reaction induced by MPTP (lower expression of microglia marker and proinflammatory interleukin). CONCLUSIONS: Cystamine exerts anti-inflammatory effects and preserves nigrostriatal function after MPTP intoxication in PD. However, further research must be conducted to provide more evidence of a protective role of cystamine in PD.