Photophobia is an abnormal intolerance of light that inducespain or discomfort in eyes. It is associated to a large number of neu-rologic and ophthalmic diseases, as headaches, dry eye or cornealneuropathy. Despite social and human impact of this disablingdisorder, neuropathogenic mechanisms of photophobia remainunknown, making it difficult to treat. Animal models are thereforefundamental to progress in our knowledge. Because photopho-bia affects 80% of patients suffering migraine, we have developeda mice model of migraine to investigate photophobia. Single orrepeated injections of isosorbide dinitrate (ISDN, a nitric oxidedonor) in C57BL/6 mice were administrated to induce migraine.Cephalic mechanical allodynia was tested by von Frey filaments tothe forehead. Light aversion was assessed by using modified ele-vated plus-maze and light/dark box tests coupled to a LED-lightingsystem. Anxiety-like behaviour was measured by the open-fieldtest. All of the animals injected developed acute or persistentmigraine-like pain. Threshold of light photosensibility was reducedafter the first ISDN injection and remained constant until 72 hafter last injection. Anxiety-like behaviour was not observed. Then,sumatriptan (only one dose 5 min after acute ISDN) or propranolol(30 min before each ISDN dose) usually used to respectively treat orprevent migraine, were administrated. Cephalic mechanical allody-nia and light aversion were abolished after sumatriptan treatment.However, propranolol prevented facial allodynia development butnot the photohypersensitivity. These findings demonstrate that (i)this model mimics migraine human features, included cephalicpain and photophobia, and (ii) the neurobiological mechanismsinvolved in the persistence of migraine and photophobia aredifferent. Our model opens up new opportunities to elucidate pho-tosensitivity mechanisms and research new therapeutic strategies.