Purpose To evaluate the effect of intraocularly applied epidermal growth factor receptor (EGFR) antibody panitumumab on axial elongation. Methods This is a preclinical, safety, and efficacy experimental study. Guinea pigs aged 2-3 weeks were fitted with bilateral plano lenses (Group I; n = 10) or underwent bilateral lens-induced myopization (LIM) (Group II; n = 10) with no intravitreal injections. Animals with LIM of Groups III (n = 15), IV (n = 15) and V (n = 15) received three 4-weekly intravitreal injections of panitumumab at doses of 25, 50 and 100 mu g, respectively, into their right eyes, and of phosphate-buffered saline into their left eyes. Results Inter-eye differences in axial elongation (right eye minus left eye at study end) decreased (p < 0.001) from 0.00 +/- 0.02 mm (Group I) and - 0.01 +/- 0.02 mm (Group II) to -0.09 +/- 0.03 mm (Group III), -0.12 +/- 0.03 mm (Group IV) and - 0.17 +/- 0.05 mm (Group V). Interocular choroidal thickness differences (measured by optical coherence tomography) increased (p < 0.01) from Groups I and II to Groups III-V. Western blot analysis showed an increase (p < 0.05) in expression levels of EGFR and its downstream phosphorylated signalling molecule, p-PI3K, in Group II compared to Group I and a decrease in Groups III-V compared to Group II (all p < 0.01). Interocular differences in retinal thickness did not differ significantly (p > 0.05) between the groups. TUNEL staining revealed no significant differences in retinal apoptotic cell density among any groups (all p > 0.05). Conclusions Intravitreally administered panitumumab in young guinea pigs with LIM resulted in a dose-dependent and treatment frequency-dependent reduction in axial elongation, supporting the role of EGFR signalling in axial elongation.