In the epigraph to his short story "Ligeia," Poe quotes the philosopher and clergyman Joseph Glanvill (1836-1880) as follows:
And the will therein lieth, which dieth not. Who knoweth the mysteries of the will, with its vigor? For God is but a great will pervading all things by nature of its intentness. Man doth not yield himself to the angels, not unto death utterly, save only through the weakness of his feeble will.
Poe was obsessed by death, especially by the fear of death, as can be seen in so many of his poems and stories. In "The Masque of the Red Death" he seems to be symbolzing the universal human fear of death and the many ways by which people try to avoid--not dying--but facing the fact of dying. With Poe this fear seems to have been heightened by his loss of faith in traditional religious beliefs, a phenomena which was becoming widespread in the Western world with the incursions of science.
"The Masque of the Red Death" seems to be intended to depict allegorically people's attempts to avoid facing the terrible fact that death will claim all of them and take away everything they own and everything they love. The refugees seal themselves up in a fortress and indulge in pleasure-seeking, with all sorts of sounds and spectacles intended primarily to distract them from thinking about the fact that everyone is dying all around them. But it is futile. Death is inescapable. He appears among them without having been impeded in the slightest by the walls and gates and claims all of them. Their luxury and revelry was all pointless and meaningless. There is no escape. The story is popular because readers easily understand the meaning behind the metaphors.
The central message of "The Masque of the Red Death" is perhaps best understood as the inevitability of death. Prospero walls himself and his courtiers inside his palace to attempt to avoid the Red Death, a horrible plague that ravages the countryside. In sharp contrast to the suffering outside, they hold a lavish costume ball. But among the costumed guests is Death himself, who has slipped in "like a thief in the night," and he strikes down first Prospero and then all of the other guests. Their wealth, power, and privilege could not save them from the inevitable, and their attempt at escaping the plague comes across as decadent and arrogant even as it is fearful. The final line of the play is chilling, and sums up the play's message succinctly: "And Darkness and Decay and the Red Death held illimitable dominion over all.’’