(A) Representative micrographs of severed wild type, parp-1(lf), and parp-2(lf) GABA motor neurons. (B) Axon regeneration in parp-1(lf) and parp-2(lf) mutants compared to wild type animals (*p<0.05, Fisher’s exact test, n = 84, 26, 61). (C) Cut axons (1) are scored for the distance they extend towards their targets in the dorsal nerve cord (2, 3, 4, 5). (D) Axon regeneration to at least 3/4 of the distance to the dorsal cord (4) is significantly increased in parp-1(lf) and parp-2(lf) mutants relative to wild type animals (*p<0.01, Fisher’s exact test, n = 61, 43, 38). (E) Axon regeneration from the cell body (2) is seen in parp-2(lf) mutants (n = 47, 32, 34). (F) Representative micrographs of injured cortical neurons exposed to negative control shRNA or PARP1 shRNA. (G) Axon regeneration is increased in murine cortical neurons lacking PARP1 (***p<0.001, ****p<0.0001, Anova with Tukey’s multiple comparisons test, n = 108, 8, 8). Axon regeneration was measured in injured cortical neurons exposed to non-coding negative control shRNA (shNC) or either of two unique PARP1 shRNAs. (H, I) Exposure to either shPARP significantly reduced PARP levels in cortical neurons relative to PARP levels in cortical neurons exposed to negative control (shNC) lentivirus (*p<0.05, **p<0.005, Anova with Tukey’s multiple comparisons test). (J) parg-1 and parg-2 loss of function incompletely suppress the increase in regeneration conferred by dlk-1(OE) (*p<0.05, relative to wild type, §p<0.05, relative to dlk-1(OE), Fisher’s exact test, n = 24, 21, 48, 62), indicating the PARGs regulate regeneration downstream of dlk-1 with at least one parallel pathway.