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Sprouty (Spry) proteins are negative feedback inhibitors of receptor tyrosine kinase signaling. Downregulation of Spry2 has been demonstrated to promote elongative axon growth of cultured peripheral and central neurons. Here, we analyzed Spry2 global knockout mice with respect to axon outgrowth in vitro and peripheral axon regeneration in vivo. Neurons dissociated from adult Spry2 deficient sensory ganglia revealed stronger extracellular signal‐regulated kinase activation and enhanced axon outgrowth. Prominent axon elongation was observed in heterozygous Spry2^+/− neuron cultures, whereas homozygous Spry2^−/− neurons predominantly exhibited a branching phenotype. Following sciatic nerve crush, Spry2^+/− mice recovered faster in motor but not sensory testing paradigms (Spry2^−/− mice did not tolerate anesthesia required for nerve surgery). We attribute the improvement in the rotarod test to higher …