Abstract: Most biochemical reactions in living cells are not closed systems; they interact with their surroundings by exchanging energy and materials. At a mesoscopic scale, the quantity of each chemical can be modeled by random time-changed Poisson processes. Understanding macroscopic behaviors is facilitated by a nonlinear reaction rate equation that describes species concentrations. In the thermodynamic limit, the large deviation rate function from the chemical master equation is governed by a Hamilton–Jacobi equation. We decompose the general macroscopic reaction rate equation into an Onsager-type strong gradient flow, supplemented by conservative dynamics. We will also present findings on the large deviation principle and the importance sampling of transition paths that connect metastable states in chemical reactions.