PACAP is a neuroprotective peptide in Parkinson’s disease models. Earlier we compared the substantia nigra of PACAP knockout (KO) and wild type mice (WT) of different ages and did not find significant changes in the cell number of dopaminergic neurons, but in ageing PACAP KO mice we detected higher number of resting microglia. Our aim was to examine the ventral tegmental area (VTA), which has important function in the regulation of social behavior.We examined the VTA of WT [n=5-5-5] and PACAP KO mice [n=5-4-5] aged 1.5,4, and 8 months. We used triple labelling, dopaminergic neurons were stained with tyrosine hydroxylase, microglia with Iba1 and we labeled the expression of specific PACAP receptor.We observed a significant age-related decline in dopaminergic neurons in both genotypes, with a more pronounced decrease in KO mice. Microglia analysis showed an age-associated reduction in cell numbers in both genotypes. The number of inactive microglia decreased in KO mice with age, on the other hand, in wild time mice the number of active microglia was reduced.We suggest that because of the age dependent dopaminergic cell loss of VTA, PACAP KO animals could show Parkinson like behavioural alterations earlier than motor symptoms. The number of microglia cells was also decreased with age in both groups, but the number of active microglia did not change in PACAP KO mice due to the lack of immunosuppressive effect of endogenous PACAP, which might also serve as a mechanism for increased dopaminergic cell death in PACAP KO animals.