Using a new labeling technique and matrix computations, this paper derives a closed formula for the number of spanning trees of a multi-star related graph G = Kn − Km(a1,a2,…,am), where Km(a1,a2,…,am) consists of m star graphs such that the ith one has a root node connected to ai leaves, and further, the m roots are connected together to form a complete graph. This result generalizes the previous result by Nikolopoulos and Rondogiannis (1998) which is limited to m = 2, 3, 4.