Summary: The author discusses and analyzes Newton’s contribution to differential equation and its development vein of differential equation thought. The results indicate that Newton laid lots of foundation on the differential equation. On the one hand, he put forward the sort of the first order differential equation for the first time and inaugurated the direction of applying infinite series to seek the solution of equation. On the other hand, he started variation of constants and applied it to solve the theory of three-body problem in advance. The academic and historical significance of the subject of differential equations are pointed out.