Early efforts to use rule-based modeling in simulation of biochemical systems include the stochastic simulation systems StochSim
A widely used tool for rule-based modeling of biochemical networks is BioNetGen  It is released under the GNU GPL, version 3. BioNetGen includes a language to describe chemical substances, including the states they can assume and the bindings they can undergo. These rules can be used to create a reaction network model or to perform computer simulations directly on the rule set. The biochemical modeling framework Virtual Cell includes a BioNetGen interpreter.
A close alternative is the Kappa language. Another alternative is BioChemical Space language.