Introduction Quinolinic acid (QA) induced striatal lesion is an important model for excitotoxicity that is also used for efficacy studies. To date, the morphological and spectroscopic indices of this model have not been studied longitudinally by MRI. Aims This study aimed to monitor the lesion progression and changes in N-acetyl aspartate (NAA) as viewed by MRI and MRSI, respectively, in vivo over a period of 49 days. Results We found that the affected areas exhibited both high and low apparent diffusion coefficients (ADC) even 49 days post QA injection in three of the six tested animals. MRI guided histological analysis correlated areas characterised by high ADCs on day 49 with cellular loss, while areas characterised by lower ADCs correlated with macrophage infiltration (CD68 positive stain). Our MRSI study revealed an initial reduction of NAA levels in the lesioned striatum, which significantly recovered with time, although not to control levels. Total striatum normalised NAA levels recovered from 0.67textpm0.15 (of the contralateral row) on day 1 to 0.90textpm0.12 on day 49. Conclusions Our findings suggest that NAA should be considered as a marker for neuronal dysfunction, in addition to neuronal viability. Some behavioural indices could be correlated to permanent neuronal damage while others demonstrated a spontaneous recovery parallel to the NAA recovery. Our findings may have implications in efficacy oriented studies performed on the QA model.