This paper deals with the construction of integro-differential polynomial splines of the fifth order on a uniform grid of nodes. It is supposed that values of function in nodes and the values of integrals over intervals are known. The properties of the left, the right and the middle integro-differential polynomial splines are investigated. The approximation with these splines is constructed on every grid interval separately. The results of numerical approximation by the left, the right, and the middle integro-differential splines show that the middle splines are preferable. Errors of approximation of the left, the right and the middle integro-differential polynomial splines of one variable of the fifth order are given. The approximation of functions of two variables is constructed using the tensor product. Numerical examples are presented.