He had already contributed The Virtuoso, in imitation of Spenser's style and stanza (1737) to the Gentleman's Magazine, and in 1738 A British Philippic, occasioned by the Insults of the Spaniards, and the present Preparations for War (also published separately).

His politics, said Dr. Samuel Johnson, were characterized by an "impetuous eagerness to subvert and confound, with very little care what shall be established," and he is caricatured in the republican doctor of Tobias Smollett's The Adventures of Peregrine Pickle.

In 1741, he left Edinburgh for Newcastle and began to call himself surgeon, though it is doubtful whether he practised, and from the next year dates his lifelong friendship with Jeremiah Dyson (1722–1776).

Dodsley thought the price exorbitant, and only accepted the terms after submitting the manuscript to Alexander Pope, who assured him that this was "no everyday writer".

His aim, Akenside tells us in the preface, was "not so much to give formal precepts, or enter into the way of direct argumentation, as, by exhibiting the most engaging prospects of nature, to enlarge and harmonize the imagination, and by that means insensibly dispose the minds of men to a similar taste and habit of thinking in religion, morals and civil life".

[1] His powers fell short of this ambition; his imagination was not brilliant enough to surmount the difficulties inherent in a poem dealing so largely with abstractions; but the work was well received.

Accordingly, he attacked the author of the Pleasures of the Imagination—which was published anonymously—in a scathing preface to his Remarks on Several Occasional Reflections, in answer to Dr Middleton ... (1744).

In 1744, he published his Epistle to Curio, attacking William Pulteney (afterwards Earl of Bath) for having abandoned his liberal principles to become a supporter of the government, and in the next year he produced a small volume of Odes on Several Subjects, in the preface to which he lays claim to correctness and a careful study of the best models.

But Akenside's arrogance and pedantry frustrated these efforts, and Dyson then took a house for him in Bloomsbury Square, making him independent of his profession by an allowance stated to have been £300 a year, but probably greater, for it is asserted that this income enabled him to "keep a chariot", and to live "incomparably well".

Writing to his friend so early as 1744, Akenside said that the intimacy had "the force of an additional conscience, of a new principle of religion",[1] and there seems to have been no break in their affection.