Abstract. For two positive integers m and n, let Pn be the open convex cone in R n(n+1)/2 consisting of positive definite n × n real symmetric matrices and let R (m,n) be the set of all m × n real matrices. In this paper, we investigate differential operators on the non-reductive homogeneous space Pn × R (m,n) that are invariant under the natural action of the semidirect product group GL(n, R) ⋉ R (m,n) on the MinkowskiEuclid space Pn × R (m,n) . These invariant differential operators play an important role in the theory of automorphic forms on GL(n, R) ⋉ R (m,n) generalizing that of automorphic forms on GL(n, R).