Aortic valve stenosis is characterized by inflammation and extracellular matrix remodelling. The aim of this study was to analyse the impact of mast cells on the occurrence of histopathological changes of aortic valves in patients with severe grade, non-rheumatic degenerative aortic valve stenosis. Valve specimens were obtained from 38 patients undergoing valve replacement. The role of mast cells was analysed by dividing the specimens into two groups, characterized by the presence (group A, N = 13) or absence of mast cells (group B, N = 25). There were no significant differences in clinical data between the two groups. In group A, T cells and macrophages were present in all aortic valves, as compared to a significantly lower proportion of valves with T cells and macrophages in group B. Valves in group A were less often calcified and hyaline-degenerated than valves in group B. There were no changes in fibrosis between the two groups. We found a positive correlation between the presence of mast cells and macrophages/T cells, a negative correlation between the presence of mast cells and calcification/ hyaline degeneration, and no correlation between the presence of mast cells and fibrosis. There was also a negative correlation between the presence of macrophages/T cells and calcification. The linear regression model identified only the presence of mast cells as an independent negative prediction value for calcification. In conclusion, mast cells might have a protective role against the development of calcification and hyaline degeneration in severe grade, non-rheumatic aortic valve stenosis.