Agrochemical risk assessment that takes into account only pesticide active ingredients without the spray adjuvants will miss important toxicity outcomes detrimental to non-target species including birds. In the present study toxicity of imidacloprid (IMI) pesticide was evaluated individually and in a mixture with polyethylene glycol (PEG-600) as adjuvant against Japanese quails. Oral intubation was used to obtain concentration-mortality data. Oral intubation was used to obtain concentration-mortality data. Treatments of quails for 24 h with different doses leading to the calculation of LC50 values. PEG enhances the pesticide efficacy and the LD50 value of IMI was 17.02 mg/Kg1, and in combination with PEG it was 15.98 mg/kg−1. In the second phase of the study, the effects of a single acute dose of IMI (1/4 LD50) individually or in a mixture with PEG has a potent effect on the activity of plasma AChE and brain monoamines transmitters. However, the addition of PEG-adjuvant to the selected insecticide has shown more toxic potential, more highly significant decreases in AChE activity and different changes in cortical monoamines concentration. In the present study the maximum significant inhibition of AChE activity, was recorded post 72 h exposure to IMI individually and 96 h in a mixture with PEG and exhibited −37.56% and −32.65% decreases, respectively. Moreover, the oral intubation of IMI individually or in a mixture with PEG caused a significant elevation in the quail cortical NE and 5-HT. The result also showed while the mixture of IMI + PEG induced the more potent effect in DA alterations, IMI individually was more effective in 5-HT changes. Our findings also indicated that PEG exposure induced remarkable changes in the studied monoamines level and the values were significant throughout the tested periods in DA. Moreover, the studied dose level was vigorously affected quail brain cerebral cortex histological structure. When administered individually or in a mixture with PEG, IMI disclosed neural congestion, neuronal degeneration, pyknosis and perivascular cuffing with glial cells.